Many diseases or conditions require administration of a constant or sustained level of a medicament or biologically active agent to provide the optimal prophylactic or therapeutic effects. This can be accomplished through a multiple dosing regimen or by employing a system that releases the medicament or biologically active agent in a sustained or controlled fashion. The two main advantages of using controlled release pharmaceutical compositions are the ability to maintain an elevated therapeutic level over a prolonged period of time and an increase in patient compliance obtained by reducing the number of doses necessary to achieve the same effect with a rapid-acting formulation.
Attempts to sustain medication levels include, for example, the use of a controlled release composition comprising biodegradable materials, such as polymeric compositions, containing the medicament. Polymeric controlled delivery has significantly improved the success of many drug therapies. In such a delivery system, pharmacokinetics and biodistribution of the active agent depend upon the physiochemical properties and/or degradation properties of the polymer carriers. The use of these polymeric compositions, for example, in the form of microparticles or microspheres, provides sustained release of medicaments.
Nonetheless, a number of issues hinder the applications of microparticle-based controlled release composition. For example, microparticles have a tendency to form aggregates which can significantly affect the properties of the controlled release composition. In addition, a large amount of solvent need to be added to a microparticle-based controlled release composition before its application, generally with a ratio of 80-90%:10-20%, respectively, which can be very problematic in situations, such as, when injecting the microparticle-based controlled release composition into a solid tumor. Furthermore, microparticles could move relatively easily within a tissue after its implantation. This makes it impractical, if not impossible, for the measurement of the drug release rate in tissues near the implantation site. Therefore, there exists a need for an improved microparticle-based controlled release composition.